Graduate School of Biomedical Science and Engineering, Korea Advanced Institute of Science and Technology, 373-1, Guseong-dong, Daejeon 305-701, Republic of Korea.
Arterioscler Thromb Vasc Biol. 2011 May;31(5):1141-50. doi: 10.1161/ATVBAHA.110.218206. Epub 2011 Mar 10.
Tremendous efforts have been made to establish effective therapeutic neovascularization using adipose tissue-derived stromal vascular fraction (SVF), but the efficiency is low, and underlying mechanisms and their interaction with the host in a new microenvironment are poorly understood.
Here we demonstrate that direct implantation of SVF derived from donor adipose tissue can create a profound vascular network through the disassembly and reassembly of blood endothelial cells at the site of implantation. This neovasculature successfully established connection with recipient blood vessels to form a functionally perfused circuit. Addition of vascular growth factors to the SVF implant improved the efficiency of functional neovasculature formation. In contrast, spheroid culture of SVF before implantation reduced the capacity of vasculature formation, possibly because of cellular alteration. Implanting SVF into the mouse ischemic hindlimb induced the robust formation of a local neovascular network and salvaged the limb. Moreover, the coimplantation of SVF prevented fat absorption in the subcutaneous adipose tissue graft model.
Freshly isolated SVF can effectively induce new vessel formation through the dynamic reassembly of blood endothelial cells and could be applied to achieve therapeutic neovascularization for relieving ischemia and preventing fat absorption in an autologous manner.
利用脂肪组织来源的基质血管成分(SVF)来实现有效的治疗性血管新生已经取得了巨大的努力,但效率仍然较低,其在新的微环境中的作用机制及其与宿主的相互作用仍知之甚少。
在这里,我们证明了直接植入供体脂肪组织来源的 SVF 可以通过在植入部位破坏和重新组装血液内皮细胞来创建一个深刻的血管网络。这种新的脉管系统成功地与受体血管建立了连接,形成了一个功能上灌注的循环。向 SVF 植入物中添加血管生长因子可提高功能性新血管形成的效率。相比之下,植入前对 SVF 进行球体培养会降低血管形成的能力,这可能是由于细胞发生了改变。将 SVF 植入小鼠缺血性后肢可诱导局部新生血管网络的强烈形成,并挽救肢体。此外,SVF 的共植入可防止皮下脂肪组织移植物模型中的脂肪吸收。
新鲜分离的 SVF 可以通过血液内皮细胞的动态重新组装有效地诱导新血管形成,并可用于以自体方式实现治疗性血管新生以缓解缺血和防止脂肪吸收。